Department of Pathology St. Jude Children's Research Hospital, Memphis, TN, USA.
Department of Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, 5NW-26, Philadelphia, PA 19104, USA.
Pathol Res Pract. 2024 Aug;260:155469. doi: 10.1016/j.prp.2024.155469. Epub 2024 Jul 14.
ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10 % of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94 %) DSRCTs with 75 % showing diffuse (>50 %) expression. ISL1 was positive in 1/10 (10 %) Ewing sarcomas (EWS), 7/13 (54 %) alveolar rhabdomyosarcoma (RMS), 14/22 (63 %) embryonal RMS, 7/14 (50 %) synovial sarcomas, 15/16 (93 %) neuroblastoma, 1/5 (20 %) Wilms tumor, 2/4 (50 %) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.
ISLET-1（ISL1）是一种 LIM 同源域转录因子。选择性的 ISL1 表达可见于神经内分泌、非神经内分泌和一些软组织肿瘤，包括促结缔组织增生性小圆细胞肿瘤（DSRCT）。我们评估了 ISL1（克隆 EP283，1:500，Cell Marque）在 288 例软组织肿瘤中的特异性，其中包括 17 例 DSRCT 及其他组织学模拟物。ISL1 的免疫组化阳性阈值设定为中等强度下>10%的肿瘤细胞核阳性。16 例 DSRCT 中有 15 例（94%）ISL1 免疫组化阳性，75%表现为弥漫性（>50%）表达。10 例尤文肉瘤（EWS）中有 1 例（10%）、13 例肺泡横纹肌肉瘤（RMS）中有 7 例（54%）、22 例胚胎性 RMS 中有 14 例（63%）、14 例滑膜肉瘤中有 7 例（50%）、16 例神经母细胞瘤中有 15 例（93%）、5 例 Wilms 瘤中有 1 例（20%）、4 例嗅神经母细胞瘤中有 2 例（50%）及 9 例 Merkel 细胞癌均为 ISL1 免疫组化阳性。其他肿瘤，包括所有 CIC::DUX4 肉瘤，均为阴性，仅 3 例平滑肌肉瘤、1 例血管肉瘤、1 例黏液样脂肪肉瘤、1 例炎性肌纤维母细胞瘤、1 例恶性外周神经鞘瘤、1 例腱膜滑膜巨细胞瘤、1 例去分化脂肪肉瘤及 1 例中胚层间叶瘤为阳性。总之，在所检测的软组织肿瘤中，ISL1 是 DSRCT 高度敏感但中度特异性的标志物，可用于区分小圆细胞模拟物，包括 EWS 和 CIC::DUX4 肉瘤。ISL1 在这些肿瘤中的致癌作用值得进一步研究。
